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Cancer: It’s a word that strikes fear when doctors pronounce it.
It is the driving force for Qingguo Wang’s life’s work.
But Wang isn’t your typical cancer researcher. He is a data scientist, and he is fighting cancer one byte at a time.
Wang is an associate professor of data science in Lipscomb’s College of Computing & Technology. Using computing technology to discover causes of and treatment for cancer is an important approach that has significant potential implications for the field.
“Studying cancer through the lens of computational science is very interesting,” says Wang. “It is also directly related to the welfare of patients. Even with all of the research that has been done, it is hard to find a cure for some cancer types. Many people still die from cancer. It’s a difficult disease. It affects many people, and still we don’t know as much as there is to know.”
“For some cancer types we actually know how to treat the patient if we know the driver mutations. But for many cancer types, we still don’t know. Research in this area is very much on-going, and it is very challenging.”
Wang says, for example, he has the computer science knowledge but is not an expert in biology. Data scientists like Wang typically use genomic data known as next generation sequencing — or NGS — to detect mutations that cause cancer. NGS allows researchers to sequence DNA and RNA quickly and cost-effectively.
The NGS process starts with cancer tissue that has been extracted from a patient. The tissue sample contains many cells. Wang says the DNA is extracted from those cells, which are then “chopped into short fragments” that each contain hundreds of nucleotides.
“We have to read the nucleotides from each fragment, and there can be hundreds of thousands of fragments,” he says. “These short fragments, were then provided to NGS machine which reads the nucleotides from each fragment.”
These readings create very large files. Wang analyze the files, which has hundreds of thousands of lines. When the files are compressed, each can be up to 200 GB, he says.
“It is big data,” admits Wang.
In Wang’s studies, tissue can be taken from multiple sites in a patient’s body as cancer often migrates to other organs once it has initially formed.
“We take the samples and do the sequencing to get a comprehensive view of the cancer in a patient,” he explains.
When Wang started to work in this field seven years ago, he says it could take up to six months from receiving the genome sequencing data to the discovery of the mutations that potentially cause the cancer. Today, with advances in technology, that can now be done in a matter of weeks.
“I am a computer scientist, so I like to play with the data,” he says.
When Wang began his academic studies in his native China, cancer research was far from his mind. He earned a Bachelor of Engineering degree in nuclear technology from Chengdu University of Technology and went to work as an engineer. He next earned a Master of Engineering in computer technology from Shanghai Jiao Tong University, and went to work as a software engineer first for Shanghai Hewlett-Packard Co. Ltd. and then for Shanghai Digital Intelligence System Tech. Co. Ltd.
As Wang launched into his career as a software engineer, he quickly realized the demanding nature of the work culture in China. He worked six days a week, from 10 a.m. to sometimes 10 p.m. each day. He said Sunday was the only day for rest.
“We work hard in China,” said Wang. “You cannot believe how hard we work. On Sundays I mostly slept because I was so exhausted. The work was not fulfilling to me. I felt like I was just a programming machine.”
Wang said he did the work he was given to do, but he wanted to know more. So, he began to “explore.” “I wanted to know more about computer science and the problems of life,” he said.
He decided he wanted a change and wanted to pursue research. So, Wang and his wife, Mian Pan, moved to the United States where he could pursue advanced degrees in computer science. It was a move that changed his life in profound ways.
Wang earned master and doctoral degrees in computer science, maintaining a perfect 4.0 GPA for each. Along the way, he discovered a way to blend his computer science knowledge with his passion to do something meaningful with it. Working as a research assistant while a student at Missouri, Wang was part of a team of students who was ranked among the best in the world at the computationally intense bioinformatics endeavor of predicting protein structure at the National Institutes of Health’s Ninth Critical Assessment of Techniques for Protein Structure Prediction contest in 2010.
Seeking to learn more, Wang accepted a three-year post-doctoral fellowship at Vanderbilt University, where he studied cancer genomics and biomedical informatics for three years. Wang and his fellow researchers analyzed genomic data and presented the mutations they found to physicians at Vanderbilt who would then examined the specimen from a biological viewpoint to determine the relevance of the mutations to cancer. While there, Wang also studied new methods of detecting abnormal events in human cancer genomes. He developed an NGS catalog and in 2012 developed the software VirusFinder to detect viruses through NGS data.
“Our collaborator at Vanderbilt once asked us if we could identify the viruses and their integration sites in the cancer genome. At the time the software and pipeline for characterizing genomic integration sites of viruses didn’t exist,” said Wang. “So, we developed the VirusFinder tool.”
“Viral infection, especially from tumorigenic viruses, is one of the leading causes of deaths worldwide. Some viruses, such as the hepatitis B virus, can fuse into a host genome to interrupt gene functions or induce chromosomal instability while other viruses rarely integrate into a host genome,” explained Wang. “Detecting the existence of viruses and, especially, their integration sites in host genomes is critical in understanding their role in disease development. Investigations of virus-host interactions could also shed light on virus-related cancers. The demand for the NGS investigation of virus-host interactions was hindered by the lack of effective NGS tools for virus detection.”
VirusFinder quickly became one of the most-used tools in the field for the identification of viruses and their integration sites in host genomes using NGS data, including whole transcriptome sequencing, whole genome sequencing, and targeted sequencing data. Today, it is used by medical researchers around the world.
Another of Wang’s work was detecting binding sites of the cancer-driving gene MYC. MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis and metabolism.
“It’s very important to study the MYC protein,” said Wang. “our collaborator at Vanderbilt discovered that this protein can bind to another protein —WDR5 — but we needed to verify that using sequencing data. It’s important to study this cancer-driving gene because it causes about 100,000 deaths in America alone every year.”
What Wang confirmed is that MYC cannot bind to the genome without WDR5. “If we can discover a small molecule to bind to the interface of WDR5 that MYC binds, we can interrupt MYC binding and might stop MYC as a driver of cancer. This is a very important piece of work,” he said.
When Wang accepted a computational engineer post at Memorial Sloan Kettering Cancer Center in New York in 2014, he began developing a pipeline for unifying information. Wang said researchers around the world sequence and analyze RNA sequencing data in different centers using different methodologies, which created a challenge when trying to compare data. He wanted to find a way to integrate data from different sources.
“We spent a year developing a pipeline to re-analyze all of the RNA samples from two national projects following the same protocol,” he recalled. “It’s a big project that is still ongoing.”
While at Sloan Kettering, Wang was also involved in another major research project studying gene androgen receptor (AR), the most prominent driver in prostate cancer. He studied one mutated AR gene, AR-V7, that can be translated into a protein product. AR-V7 has a significant impact on the survival of prostate cancer patients. “It’s important to detect this variant,” he said. Wang spent months developing a pipeline to detail this variant. The results of this research were incorporated in a highly cited paper published in Cell journal.
Wang believes strongly in the importance of applying computational science into cancer research. He said over the last decade significant progress has been made in utilizing computing technology in biomedical research.
“Before NGS we could only focus on cancer on a small scale or in certain regions of a genome,” he said. “It was also very costly to conduct this kind of research.”
“With the advancement in computational science as well as NGS technologies and their increasingly widespread applications to cancer research today we can do larger-scale research, decreasing cost and expediting solutions for making an impact on fighting cancer,” said Wang. Although there are still challenges to work through, integrating computational science into biomedical research has had a tremendous impact and will continue to in the future.
Wang’s work has been on the front lines of research and technology, and he continues his research in this area today. His findings have been published in numerous journals, reports and books and he has presented at many national conferences.
“Different hospitals used different cancer panels and data sharing and privacy were all barriers for cancer research,” said Wang. “By using big data and sharing that data we can find ways to improve cancer treatment. Data sharing will continue to be critically important for entire communities to find cures for cancer — to share information across different researchers, hospitals and countries — and to save lives.”
After Sloan Kettering, the next stop on Wang’s journey was Lipscomb University. But it wasn’t a stop that Wang planned.
“I thought it would be impossible for me to work at Lipscomb University,” he recalled. “I had ten years of research training. My plan was to keep researching and publishing. But God opened the door.”
To understand the significance of this part of Wang’s story, one has to go back to the summer of 2005 when he left Shanghai, China, and arrived in Columbia, Missouri. He had no vehicle. He knew few people. But an encounter in the first few days in the United States had a profound impact on Wang’s life.
“I had my first encounter with Christianity,” he recalled.
The Missouri campus was far from Wang’s apartment. During the week, he took the city bus to the campus. But the bus didn’t run on weekends near his apartment. Wang’s wife Mian Pan connected with a minister Paul Fox who lived nearby who drove to campus on the weekends and let him ride along.
One day Wang overslept. Fox knocked on their door and headed to campus when he got no response. Wang woke up, realized what happened and called the Foxes’ house. His wife answered the phone and said he would come get them.
“He knocked on the door and was very sweaty from the summer heat,” he said. “Sweat was dripping from him. I was so moved. In China even very good friends hesitate to help sometimes. But this man, who we had only known for a few days, gladly provided help. And he was a Christian. So, that’s my first impression of a Christian.”
Wang realized after the fact that Fox had already gotten to campus and came all the way back to get him.
Another person they met in Columbia who worked with a Chinese church often invited Chinese students to his home for holiday meals.
“He would say ‘it’s a great blessing to have these students in my home,’” Wang said. “It moved me because we as international students … we didn’t have money. We didn’t know important people and didn’t have a high status. We had F1 visas, which meant we couldn’t work full time. Basically we were the poorest among the poor. But when he said it was a great blessing to have us in his home that moved me.”
“The Chinese culture is different in that status is very important. But for many Christians, they don’t care about status. They try to get to know the people they meet. This was something I really enjoyed and really love,” he continued. “That’s one reason I converted to the Christian faith a year after I came to the U.S.”
When Wang came to Nashville in 2011 for his work at Vanderbilt, he began worshipping at Middle Tennessee Chinese Church of Christ, which meets at Natchez Trace Church of Christ near the university. Before Wang left for Sloan Kettering in 2014, the minister at Middle Tennessee Chinese Church of Christ wrote to Fortune Mhlanga, dean of Lipscomb University’s College of Computing & Technology, to ask if there was an opening for Wang.
“I had already accepted a position in New York,” Wang recalled. “But I promised Fortune I would keep in touch and would come and give a talk to students.”
At the end of 2015, Wang contacted Mhlanga, who asked him to consider interviewing for a faculty position in the College of Computing & Technology. Mhlanga set the interview for a Thursday in Nashville, and every Thursday Wang was committed to a lab meeting in New York at Sloan Kettering.
“At that time, I didn’t want my boss to know that I was interviewing,” he said. “He would think that I wanted to leave, and at the time I didn’t. So I asked God that if He wanted me to come to the interview to help me so I could go without my boss knowing.”
The week before the interview, his boss at Sloan Kettering announced that the weekly Thursday lab meetings would be held on Tuesdays beginning that week.
“Then I prayed more than 10 things about the interview,” he said. “Although at that time I didn’t know if I could work at Lipscomb, I still wanted to prepare well for the interview. On all of those 10 things, I saw God answer my prayer. The interview went very well.”
Although Wang was happy at Sloan Kettering, he began thinking seriously about working at Lipscomb. In New York, he was one of many researchers. At Lipscomb, he was unique.
“At Lipscomb I could be more useful,” he admitted. “God can use my skills. At Sloan Kettering I was useful to a small group of people around me. But at Lipscomb I could teach students and help many more people.”
“It was a big decision to be here. But I saw God open the door to Lipscomb University. His will is very clear to me.”
Today, Wang prepares the next generation of data scientists in the classroom and as they work alongside him in his research to help find a cure for cancer, one byte at a time.